Cancer is a worldwide problem. Finding novel compositions and methods for the treatment of cancer is of vital interest. The treatment of cancer falls into three general categories: chemotherapy, radiation therapy and surgery. Often, therapies are combined since a combination of therapies increases the probability the cancer will be eradicated as compared to treatment strategies utilizing a single therapy. Typically, the surgical excision of large tumor masses is followed by chemotherapy and/or radiation therapy.
Metals, such as magnesium, iron, and cobalt, play essential cellular roles in biological systems by performing catalytic roles in biochemical reactions. However, other metals including copper, gold, and platinum possess unique properties, such as redox reactivity, Lewis acidity, variable coordination modes, and reactivity towards biological macromolecules that can unleash lethal effects on cells. The toxicity of these metals can, under certain conditions, be controlled and subsequently used to efficiently kill cells that are associated with pathogenic conditions, such as cancer. One important example is the widespread use of platinum-containing compounds, such as cisplatin which damage DNA and induce apoptosis in various cancer cell lines.
Gold(I) complexes are gaining attention for their favorable toxicity toward malignant cells. Gold(I) is a compact, soft Lewis acid that stably binds cysteinate, selenocysteinate, and (less so) histidine residues. Auranofin, a triethylphosphine complex of Au(I), is used to treat rheumatoid arthritis. Despite this therapeutic use, auranofin causes immunosuppression by inhibiting T-cell proliferation. In addition, auranofin produces cytostatic and cytotoxic effects against various cancer cells in vitro. However, the mechanism accounting for auranofin's cytotoxicity differs from cisplatin as the gold(I) compound does not directly damage DNA. Auranofin and related gold(I) compounds induce cell death through effects on mitochondrial integrity including swelling and decreases in mitochondrial membrane potential. These effects are believed to be related to the inhibition of mitochondrial thioredoxin reductase caused by the binding of gold(I) to the active site selenocysteinate.